温肺化纤汤介导Wnt经典信号通路调控骨髓间充质干细胞向Ⅱ型肺泡细胞分化的机制研究

项目名称： 温肺化纤汤介导Wnt经典信号通路调控骨髓间充质干细胞向Ⅱ型肺泡细胞分化的机制研究

项目编号： No.81460708

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘良徛

作者单位： 江西中医药大学

项目金额： 49万元

中文摘要： 临床研究证实温肺化纤汤治疗肺纤维化疗效显著，基础研究显示其能动员大鼠自身骨髓间充质干细胞（BMSCs）向病变部位迁移，发挥修复作用。但BMSCs在肺部定植后，如何分化为目标细胞以替代损伤细胞的过程不清楚。Ⅱ型肺泡细胞增殖并向Ⅰ型肺泡细胞转分化是肺损伤修复的唯一途径，Wnt经典信号通路在BMSCs分化中起重要作用。据此，我们提出温肺化纤汤可能通过抑制Wnt经典信号通路激活下游靶基因的转录，促进BMSCs向Ⅱ型肺泡细胞分化的假说。本研究引入GFP转基因BMSCs嵌合SD大鼠模型，运用基因芯片、Western blot 等技术，采用动物和细胞实验相结合，筛选Wnt经典信号通路中调控BMSCs向Ⅱ型肺泡细胞分化过程中的靶基因；观察温肺化纤汤干预Wnt经典信号通路相关因子的表达和活性，揭示Wnt经典信号通路在BMSCs向Ⅱ型肺泡细胞定向分化中的作用及温肺化纤汤的调节机制，为临床应用提供实验依据。

中文关键词： 中药复方；肺纤维化；信号通路；实验研究

英文摘要： Clinical studies have confirmed that Wenfeihuaxian formula has good curative effect on pulmonary fibrosis. The lab research showed that Wenfeihuaxian formula can effectively mobilized autologous bone marrow mesenchymal stem cells(BMSCs) of rats migrating to repair pulmonary fibrosis lesion after BMSCs planting in the lung. But the procedure of how BMSCs differentiate into target cells to replace the damaged cells is still unclear. The type Ⅱ alveolar cell is main stem cells in lungs.The type Ⅱ alveolar cell's proliferation and differentiation into type I alveolar cells are only way to repair lung injury. Wnt classic signaling pathway plays an important role in the differentiation of BMSCs. Therefore, we propose Wenfeihuaxian formula promote differentiation of BMSCs into type II alveolar cells by inhibiting Wnt classic signaling pathway activates the transcription of downstream target genes hypothesis. This research plan to establish the SD rat pulmonary fibrosis model jointed with GFP-BMSCs. Then we will screening the target genes in Wnt classic signal pathway which regulate BMSCs differentiate to type Ⅱ alveolar cells by using PCR gene chip and Western blot. We also reveal the role of Wnt classic signaling pathway in that process by investigating the Wenfeihuaxian formula intervention on expression and biological activity of key genes in Wnt classic signaling pathway. So we will provide objective experimental clinical evidence for Wenfeihuaxian formula.

英文关键词： Traditional Chinese Medicine formula;pulmonary fibrosis;signaling pathway;experimental research